title: Mutation and copy number analysis of LNX1 and Numbl in nervous system tumors.
abstract: Alterations at chromosome locus 4q12 are frequently found in gliomas; this locus contains the receptor tyrosine kinase--encoding genes KIT, PDGFRA, and KDR (alias VEGFR2). Notable among the genes at this locus is LNX1, the ligand of Numb protein X. LNX1 encodes a PDZ domain containing protein, which interacts with the cell fate determinant Numbl, a Numb homolog-like gene involved in the maintenance of neural progenitor cells during embryonic neurogenesis. We performed a mutation analysis for LNX1 and Numbl genes. In addition, gene copy numbers of LNX1, Numbl, and KIT in human nervous system tumors were analyzed by chromogenic in situ hybridization. Tissue samples from 90 patients were screened for LNX1 and Numbl mutations, and tissue sections from 56 samples were analyzed for gene amplification status. Our analysis revealed missense mutations in LNX1 exons 3 and 5 and a single-nucleotide polymorphism in Numbl exon 6. In addition, polyglutamine repeat polymorphism was found in Numbl exon 10. Chromogenic in situ hybridization showed gene amplification of LNX1 in 10%, Numbl in 5%, and KIT in 6% of nervous system tumors. Both gene sequence alterations and amplifications of LNX1 and Numbl are present in a subset of human gliomas, and the role of these genes in neurogenesis suggests that they may contribute to development of glial tumors.
authors.affiliation: Molecular Cancer Biology Program, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 63, FIN-00014 University of Helsinki, Finland. Tea.Blom@helsinki.fi
authors.forename: Tea
authors.initials: T
authors.lastname: Blom
authors.forename: Annariikka
authors.initials: A
authors.lastname: Roselli
authors.forename: Minna
authors.initials: M
authors.lastname: Tanner
authors.forename: Nina N
authors.initials: NN
authors.lastname: Nupponen
mesh_terms: D005091:Exons; D018628:Gene Dosage; D005910:Glioma / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation; D009423:Nervous System Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C530266:NUMBL protein, human; C484733:LNX1 protein, human; D044767:Ubiquitin-Protein Ligases; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha